Beyond biologic sex: Exploratory insights into the heterogeneity of hormonal and contextual drivers of periodontal and peri-implant outcomes.

Abstract

Background: Periodontal and peri-implant diseases are multifactorial inflammatory conditions influenced by microbial, host, hormonal, genetic, and behavioral factors. Although sex-based differences in immune and inflammatory responses are well recognized in medicine, the extent to which biologic sex and hormonal status influence the prevalence, severity, and biologic markers of periodontal and peri-implant diseases remains unclear.

Objective: This narrative review synthesizes available human and animal evidence to evaluate whether sexual dimorphism exists in periodontal disease and peri-implant disease expression and to synthesize available evidence regarding hormonal status and biologic markers as potential modifying factors.

Methods: A comprehensive literature search was conducted to identify human and animal studies evaluating sex-associated differences in periodontal disease, peri-implant mucositis, and peri-implantitis. Sixty-eight human studies and 29 animal studies were included. Human studies encompassed epidemiologic, clinical, and biomarker-based investigations, while animal studies included direct male-female comparisons and female-only hormonal deficiency models.

Results: Most population-based human studies reported a higher prevalence or severity of periodontitis in males, characterized by greater clinical attachment loss and probing depths. However, several studies - particularly those involving adolescents - reported no sex differences, and a minority demonstrated female-predominant gingival inflammation, often in hormonally active life stages. In peri-implant disease, findings were largely inconsistent, with most studies reporting no significant association between biologic sex and peri-implantitis, while smaller subsets identified either male or female sex as a potential risk factor. Animal studies demonstrated heterogeneous sex-associated outcomes in direct male-female comparisons. In contrast, female-only estrogen-deficiency models consistently showed increased periodontal destruction and impaired peri-implant bone remodeling.

Conclusion: Current evidence does not support uniform or universal sexual dimorphism in periodontal or peri-implant disease. Rather, the available literature remains heterogenous and largely exploratory, with observed differences varying according to hormonal status, age, inflammatory profile, and behavioral and environmental exposures. Across both human and animal studies, estrogen deficiency emerged as a consistent modifier of periodontal and peri-implant outcomes across species. Future studies incorporating prospective hormonal stratification, biologic-marker analysis, and large-scale epidemiologic datasets may help clarify multifaceted risk patterns.